A desilylative approach to alkyl substituted C(1)-ammonium enolates: application in enantioselective [2+2] cycloadditions

Yihong Wang; Claire Mary Young; Honglei Liu; Will Hartley; Max Wienhold; David Bradford Cordes; Alexandra Martha Zoya Slawin; Andrew David Smith

doi:10.1002/anie.202208800

A desilylative approach to alkyl substituted C(1)-ammonium enolates: application in enantioselective [2+2] cycloadditions

Yihong Wang, Claire Mary Young, Honglei Liu, Will Hartley, Max Wienhold, David Bradford Cordes, Alexandra Martha Zoya Slawin, Andrew David Smith^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The catalytic generation of C(1)-ammonium enolates from the corresponding α-silyl-α-alkyl substituted carboxylic acids using the isothiourea HyperBTM is reported. This desilylative approach grants access to α-unsubstituted and α-alkyl substituted C(1)-ammonium enolates, which are typically difficult to access through traditional methods reliant upon deprotonation. The scope and limitations of this process is established in enantioselective [2+2]-cycloaddition processes with perfluoroalkylketones (31 examples, up to 96% yield and >99:1 er), as well as selective [2+2]-cycloaddition with trifluoromethyl enones (4 examples, up to 75% yield and >99:1 er). Preliminary mechanistic studies indicate this process proceeds through an initial kinetic resolution of an in situ prepared (±)-α-silyl-α-alkyl substituted anhydride, while the reaction process exhibits overall pseudo zero-order kinetics.

Original language	English
Article number	e202208800
Number of pages	9
Journal	Angewandte Chemie International Edition
Volume	61
Issue number	38
Early online date	8 Aug 2022
DOIs	https://doi.org/10.1002/anie.202208800
Publication status	Published - 12 Sept 2022

Keywords

B-lactone
Cycloaddition
Desilyation
Enolate
Isothiourea

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10.1002/anie.202208800Licence: CC BY

Wang-2022-A-desilylative-approach-to-alkyl-ACIE-08800-CCBY
Copyright © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Final published version, 9.69 MBLicence: CC BY

Honglei Liu - Newton Fellowship: Dynamic Kinetic Resolution/Desynnetrisation of Atropisomeric Biaryl Diols Using Isothioureas
Smith, A. (PI)
The Royal Society
1/02/18 → 31/01/20
Project: Fellowship

data underpinning "A Desilylative Approach To Alkyl Substituted C(1)-ammonium Enolates: Application In Enantioselective [2+2] Cycloadditions"
Smith, A. D. (Creator), Wang, Y. (Owner) & Young, C. M. (Creator), University of St Andrews, 20 Jul 2022
DOI: 10.17630/941e041b-bfd5-4ccf-ba56-0c72af3eceee, http://hdl.handle.net/10023/26954
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Cite this

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title = "A desilylative approach to alkyl substituted C(1)-ammonium enolates: application in enantioselective [2+2] cycloadditions",

abstract = "The catalytic generation of C(1)-ammonium enolates from the corresponding α-silyl-α-alkyl substituted carboxylic acids using the isothiourea HyperBTM is reported. This desilylative approach grants access to α-unsubstituted and α-alkyl substituted C(1)-ammonium enolates, which are typically difficult to access through traditional methods reliant upon deprotonation. The scope and limitations of this process is established in enantioselective [2+2]-cycloaddition processes with perfluoroalkylketones (31 examples, up to 96% yield and >99:1 er), as well as selective [2+2]-cycloaddition with trifluoromethyl enones (4 examples, up to 75% yield and >99:1 er). Preliminary mechanistic studies indicate this process proceeds through an initial kinetic resolution of an in situ prepared (±)-α-silyl-α-alkyl substituted anhydride, while the reaction process exhibits overall pseudo zero-order kinetics.",

keywords = "B-lactone, Cycloaddition, Desilyation, Enolate, Isothiourea",

author = "Yihong Wang and Young, {Claire Mary} and Honglei Liu and Will Hartley and Max Wienhold and Cordes, {David Bradford} and Slawin, {Alexandra Martha Zoya} and Smith, {Andrew David}",

note = "Funding: The research leading to these results has received funding from the CSC-St Andrews PhD Scholarship Scheme (Y.W.), the Newton Fellowship Programme (H.L.) and the Engineering and Physical Sciences Research Council, University of St Andrews, and the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT) for financial support [Ph.D. studentship to W. H.; Grant code: EP/L016419/1].",

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language = "English",

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T1 - A desilylative approach to alkyl substituted C(1)-ammonium enolates

T2 - application in enantioselective [2+2] cycloadditions

AU - Wang, Yihong

AU - Young, Claire Mary

AU - Liu, Honglei

AU - Hartley, Will

AU - Wienhold, Max

AU - Cordes, David Bradford

AU - Slawin, Alexandra Martha Zoya

AU - Smith, Andrew David

N1 - Funding: The research leading to these results has received funding from the CSC-St Andrews PhD Scholarship Scheme (Y.W.), the Newton Fellowship Programme (H.L.) and the Engineering and Physical Sciences Research Council, University of St Andrews, and the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT) for financial support [Ph.D. studentship to W. H.; Grant code: EP/L016419/1].

PY - 2022/9/12

Y1 - 2022/9/12

N2 - The catalytic generation of C(1)-ammonium enolates from the corresponding α-silyl-α-alkyl substituted carboxylic acids using the isothiourea HyperBTM is reported. This desilylative approach grants access to α-unsubstituted and α-alkyl substituted C(1)-ammonium enolates, which are typically difficult to access through traditional methods reliant upon deprotonation. The scope and limitations of this process is established in enantioselective [2+2]-cycloaddition processes with perfluoroalkylketones (31 examples, up to 96% yield and >99:1 er), as well as selective [2+2]-cycloaddition with trifluoromethyl enones (4 examples, up to 75% yield and >99:1 er). Preliminary mechanistic studies indicate this process proceeds through an initial kinetic resolution of an in situ prepared (±)-α-silyl-α-alkyl substituted anhydride, while the reaction process exhibits overall pseudo zero-order kinetics.

AB - The catalytic generation of C(1)-ammonium enolates from the corresponding α-silyl-α-alkyl substituted carboxylic acids using the isothiourea HyperBTM is reported. This desilylative approach grants access to α-unsubstituted and α-alkyl substituted C(1)-ammonium enolates, which are typically difficult to access through traditional methods reliant upon deprotonation. The scope and limitations of this process is established in enantioselective [2+2]-cycloaddition processes with perfluoroalkylketones (31 examples, up to 96% yield and >99:1 er), as well as selective [2+2]-cycloaddition with trifluoromethyl enones (4 examples, up to 75% yield and >99:1 er). Preliminary mechanistic studies indicate this process proceeds through an initial kinetic resolution of an in situ prepared (±)-α-silyl-α-alkyl substituted anhydride, while the reaction process exhibits overall pseudo zero-order kinetics.

KW - B-lactone

KW - Cycloaddition

KW - Desilyation

KW - Enolate

KW - Isothiourea

U2 - 10.1002/anie.202208800

DO - 10.1002/anie.202208800

M3 - Article

SN - 1433-7851

VL - 61

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 38

M1 - e202208800

ER -

A desilylative approach to alkyl substituted C(1)-ammonium enolates: application in enantioselective [2+2] cycloadditions

Abstract

Keywords

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Projects

Honglei Liu - Newton Fellowship: Dynamic Kinetic Resolution/Desynnetrisation of Atropisomeric Biaryl Diols Using Isothioureas

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data underpinning "A Desilylative Approach To Alkyl Substituted C(1)-ammonium Enolates: Application In Enantioselective [2+2] Cycloadditions"

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